Reproductive Immunology


Reproductive immunology is an interdisciplinary science, which deals with the role of immunocytes and cytokines in reproduction and, as a consequence, immune control of fertility and sexually transmitted diseases. In this article, we briefly discuss Veterinary Reproductive Immunology and then go back to the triggering concepts and focus on the foetus as an allograft paradox, if any (alternate theories to the self/non‐self vision of immunity, for which viviparity is not a problem, are dealt with). We then deal with various aspects of the materno‐foetal relationship at cellular and molecular level, both in the established pregnancy and at implantation. This leads us to discuss implantation failure(s) and recurrent spontaneous abortion as well as immune control of fertility and control of STDs.

Key Concepts

  • The foetus is usually seen as an allograft in mother's womb, which should be rejected by maternal immune system.
  • The placental (allo) antigenicity is severely reduced.
  • A complex cytokinic network specifically regulates some aspects of maternal immunity while sparing trophic and angiogenic circuits.
  • Uterine natural killer cells are a specialised subset with limited cytotoxicity but trophic, immunoregulatory and angiogenic properties.
  • Deregulations of the cytokinic uterine environment can lead to sterility.
  • Regulatory T cells are important in placental pregnancy, and their deletion enhances pregnancy loss.
  • Immune interception of fertility is feasible.

Keywords: reproduction; immunology; contraception; infertility; diseases

Figure 1. The human placenta.
Figure 2. The CBA × DBA/2 murine abortion system: CBA/J (H‐2k) females mated with DBA/2 (H‐2d) females exhibit a high rate of foetal resorptions not seen when mated with BALB/c males (also H‐2d) nor in other matings (such as CBA/J × CBA/J, BALB/c × BALB/C and C3He × DBA/2 – also H‐2k × H‐2d). Pre‐immunisation of the CBA/J mother with paternal MHC compatible, minor loci disparate BALB/c splenocytes correct resorption rates.
Figure 3. Implantation steps.
Figure 4. Two possible immune defects in implantation. Lack of proper (inflammatory) cytokine production leads to adhesion defects, but conversely an excess of some of these will activate NK cells towards a cytostatic/cytotoxic/procoagulant pathway and induce early foetal losses or first trimester abortion.
Figure 5. The TH1:TH2 paradigm.
Figure 6. One of the mechanisms of HIV‐1 transmission from mother to child: fusion of infected lymphocytes with trophoblasts (here the BeW0 choriocarcinoma cell line).


Bartocci A, Pollard JW and Stanley ER (1986) Regulation of colony stimulating factor 1 during pregnancy. Journal of Experimental Medicine 164: 956–961.

Martal J, Assal NE, Assal Meliani A, et al. (1993) Immunoendocrine properties of tau interferons in the maternal recognition of pregnancy. In: Glasser SR, (ed). Endocrinology of Embryo Endometrium Interactions, pp. 195–216. International Ciba Foundation Symposium, Congress of Endocrinology, Bordeaux, New York: Plenum Press.

Munn DH, Zhou M, Attwood JT, et al. (1998) Prevention of allogeneic foetal rejection by tryptophan catabolism. Science 281: 1191–1193.

Rossant J, Mauro VM and Croy BA (1982) Importance of trophoblast genotype for survival of interspecific murine chimeras. Journal of Embryology and Experimental Morphology 69: 141–168.

Samstein RM, Josefowicz SZ, Arvey A et al. (2012) Extrathymic generation of regulatory T cells in placental mammals mitigates maternal‐fetal conflict. Cell 150 (1): 29–38.

Talwar GP (2013) Making of a vaccine preventing pregnancy without impairment of ovulation and derangement of menstrual regularity and bleeding profiles. Contraception 87 (3): 280–287.

Toullet F and Voisin GA (1969) Réactions d'hypersensibilité et anticorps sériques envers les auto antigènes de spermatozoïdes; Relations avec le mécanisme de l'orchite aspermatogénétique auto‐immune. Annales de l'Institut Pasteur 116: 579–601.

Wegmann TG (1984) Foetal protection against abortion: is it immunosuppression or immunostimulation? Annales d'Immunologie de l'Institut Pasteur 135: D309.

Wegmann TG, Lin H, Guilbert L and Mossman TH (1993) Bidirectional cytokine interactions in the maternal‐fetal relationship: is successful pregnancy a TH2 phenomenon. Immunology Today 14 (7): 353–356. (Review)

Further Reading

Aitken RJ (2002) Immunocontraceptive vaccines for human use. Journal of Reproductive Immunology 57 (1–2): 273–287.

Baines MG and Gendron RL (1993) In: Chaouat G, (ed). Natural and Experimental Animal Models of Reproductive Failure in Immunology of Pregnancy, pp. 173–203. Boca Raton, FL: CRC Press.

Casper C and Fenyo EM (2001) Mother‐to‐child transmission of HIV‐1: the role of HIV‐1 variability and the placental barrier. Acta Microbiologica et Immunologica Hunganca 48 (3–4): 545–573.

Chaouat G, Ledée‐Bataille N, Dubanchet S, et al. (2004) Th1/Th2 paradigm in pregnancy: paradigm lost? Cytokines in pregnancy/early abortion: re‐examining the Th1/Th2 paradigm. International Archives in Allergy Immunology 134: 93–119.

Croy BA (2014) Reproductive immunology issue one: cellular and molecular biology. Cellular & Molecular Immunology 11: 405–406.

Croy BA (2014) Reproductive immunology issue 2: cellular and molecular biology. Cellular & Molecular Immunology 11: 503–505.

Croy BA, Chantakru S, Esadeg S, Ashkar AA and Wei Q (2002) Decidual natural killer cells: key regulators of placental development (a review). Journal of Reproductive Immunology 57 (1–2): 151.

Dolcini G, Derrien M, Chaouat G, Barre‐Sinoussi F and Menu E (2003) Cell‐free HIV type 1 infection is restricted in the human trophoblast choriocarcinoma BeWo cell line, even with expression of CD4, CXCR4 and CCR. AIDS Research and Human Retroviruses 19 (10): 857–864.

Douglas GC, Fazely F and Hu JJ (1998) Transmission of HIV to the placenta, fetus and mother and implications of gametic infection. Journal of Reproductive Immunology 1 (1–2): 21–29.

Ferro VA (2002) Current advances in antifertility vaccines for fertility control and noncontraceptive applications. Expert Reviews in Vaccines 1 (4): 443–452.

Le Bouteiller P, Legrand‐Abravanel F and Solier C (2003) Soluble HLA‐G1 at the materno‐foetal interface: a review. Placenta 24 (suppl. A): S10–S15.

Loke YW and King A (1995) Human Implantation: Cell Biology and Immunology. Cambridge: Cambridge University Press.

Menu E, Scarlatti G, Barre‐Sinoussi F, et al. (2003) International Workshop. Mother‐to‐child transmission of HIV: developing integration of healthcare programmes with clinical, social and basic research studies. Report of the International Workshop held at Chobe Marina Lodge, Kasane, Botswana, 21–25 January 2003. Acta Paediatrica 2 (11): 1343–1348.

Moussa M, Mognetti B, Dubanchet S, et al. (1999) Vertical transmission of HIV: parameters which might affect infection of placental trophoblasts by HIV‐1: a review. Biomed group on the study of in utero transmission of HIV‐1. American Journal of Reproductive Immunology 41 (5): 312–319.

Raghupathy R (1997) Th1‐type immunity is incompatible with successful pregnancy. Immunology Today 18 (10): 478–482.

Ruocco MG, Chaouat G, Florez L, Bensussan A and Klatzmann D (2014) Regulatory T cells in pregnancy: historical perspective, state of the art, and burning questions. Frontiers in Immunology 5: 389.

Toth FD, Bacsi A, Beck Z and Szabo J (2001) Vertical transmission of human immunodeficiency virus. Acta Microbiologica et Immunologica Hunganca 48 (3–4): 413–427.

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How to Cite close
Chaouat, Gérard(Apr 2015) Reproductive Immunology. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000966.pub2]